Low-Intensity Exercise Modulates Gut Microbiota to Fight Against Radiation-Induced Gut Toxicity in Mouse Models

Abstract

Radiation-induced gastrointestinal (GI) tract toxicity halts radiotherapy and degrades the prognosis of cancer patients. Physical activity defined as “any bodily movement produced by skeletal muscle that requires energy expenditure” is a beneficial lifestyle modification for health. Here, we investigate whether walking, a low-intensity form of exercise, could alleviate intestinal radiation injury. Short-term (15 days) walking protected against radiation-induced GI tract toxicity in both male and female mice, as judged by longer colons, denser intestinal villi, more goblet cells, and lower expression of inflammation-related genes in the small intestines. High-throughput sequencing and untargeted metabolomics analysis showed that walking restructured the gut microbiota configuration, such as elevated Akkermansia muciniphila, and reprogramed the gut metabolome of irradiated mice. Deletion of gut flora erased the radioprotection of walking, and the abdomen local irradiated recipients who received fecal microbiome from donors with walking treatment exhibited milder intestinal toxicity. Oral gavage of A. muciniphila mitigated the radiation-induced GI tract injury. Importantly, walking did not change the tumor growth after radiotherapy. Together, our findings provide novel insights into walking and underpin that walking is a safe and effective form to protect against GI syndrome of patients with radiotherapy without financial burden in a preclinical setting.

Stable colonization of Akkermansia muciniphila educates host intestinal microecology and immunity to battle against inflammatory intestinal diseases

“…Although our previous study identified the protective effect of A. muciniphila against intestinal radiation injuries 26 , some individuals always showed an unsatisfactory response (Supplementary Fig. 9 ).…”

“…Akkermansia muciniphila ( A. muciniphila ) is a potential probiotic and has been proven to fight against colorectal cancer and many metabolic diseases 24 , 25 . In our previous study, although A. muciniphila alleviated intestinal radiation injuries in mouse models, some individuals always experienced unsatisfactory therapeutic effects 26 . Whether the colonization of probiotics dictates their therapeutic efficacy and how monobacterial preparation optimizes the gut microhabitats remain poorly understood.…”

Biomodified Extracellular Vesicles Remodel the Intestinal Microenvironment to Overcome Radiation Enteritis

“…Ionizing radiation has been used in many fields, like chest X-ray, computed tomography (CT) and radiation therapy. Radiotherapy, as the most effective cytotoxic treatment, is used to cure more than 50% of cancer patients throughout the world . Nevertheless, people subjected to ionizing radiation, such as radiology technologists, radiologists and particularly cancer patients, always develop a series of clinical complications, including toxicity in the bone marrow (hematopoietic syndrome) and GI symptoms. ,, A previous study demonstrated that the small intestine, which is the largest organ in the body and exhibits a higher sensitivity to ionizing radiation, is the major site of damage during irradiation. , Despite having the highest self-renewal rate of the intestinal epithelium, acute radiation injury of intestine may facilitate mucosal epithelium injury, leading to malabsorption, diarrhea, bacterial influx, sepsis, and even death. , Hence, radiation-induced gastrointestinal damage, especially small intestine injury, is a severe problem that needs to be effectively treated for people suffering from IR exposure.…”

Social Hierarchy Dictates Intestinal Radiation Injury in a Gut Microbiota-Dependent Manner

“…Next, we aimed to screen for the gut microbe which was able to mitigate intestinal radiation injury in high-ranking mice. For the monoassociation study, Lactobacillus murinus ( L. murinus ) was selected due to (i) its recognition as a classic probiotic [ 35 , 36 ], (ii) its presence as the dominant gut strain in both Dom and Sub mice ( Figure 1 F and Figure 5 A,B), (iii) its significant reduction in frequency in Dom mice after TAI ( Figure S5A ). We clarified the radioprotective function of L. murinus in mice without social hierarchy, which have been most frequently used in traditional research ( Figure 5 C).…”